An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism
Abstract Dysbiosis of gut microbiota significantly exacerbates the progression of rheumatoid arthritis (RA). Targeting gut microbiota may present a promising therapeutic strategy for RA. Gold nanospheres (GNS), known for excellent biocompatibility, stability and minimal toxicity, have emerged as pre...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03450-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850269147781398528 |
|---|---|
| author | Chuan Yang Langlang Xie Zihan Deng Hongbo Ai Tingwen Xiang Xiaojing Yan Zhiguo Ling Shiyu Xiao Yong Tang Gang Huang Fei Luo Yueqi Chen |
| author_facet | Chuan Yang Langlang Xie Zihan Deng Hongbo Ai Tingwen Xiang Xiaojing Yan Zhiguo Ling Shiyu Xiao Yong Tang Gang Huang Fei Luo Yueqi Chen |
| author_sort | Chuan Yang |
| collection | DOAJ |
| description | Abstract Dysbiosis of gut microbiota significantly exacerbates the progression of rheumatoid arthritis (RA). Targeting gut microbiota may present a promising therapeutic strategy for RA. Gold nanospheres (GNS), known for excellent biocompatibility, stability and minimal toxicity, have emerged as precise modulators of gut microbiota, reshaping intestinal environments to treat various inflammatory diseases. Our study found that oral administration of 60-nm GNS effectively ameliorated collagen-induced arthritis (CIA) in mice, with a marked reduction in disease severity and synovial inflammation. Specifically, GNS notably enriched the probiotic genus Ligilactobacillus while restoring intestinal barrier function by upregulating tight junction proteins Claudin-1 and ZO-1. Targeted metabolomics analysis revealed GNS substantially increased the production of indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in gut, which were shown to activate the aryl hydrocarbon receptor (AhR) pathway. Mechanistic studies demonstrated that the IPA/IAA mixture inhibited PTEN ubiquitination, stabilizing PTEN protein levels and suppressing NF-κB activation in synovial tissues. These changes correlated with reduced synovial hyperplasia and inflammatory infiltration. Our findings established GNS as an effective nanomodulator of the gut-joint axis, providing novel insights into microbiota-targeted therapies for RA and other inflammatory diseases. Graphical abstract |
| format | Article |
| id | doaj-art-506617fa4dbf46069924d449a890d020 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-506617fa4dbf46069924d449a890d0202025-08-20T01:53:15ZengBMCJournal of Nanobiotechnology1477-31552025-05-0123112210.1186/s12951-025-03450-7An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolismChuan Yang0Langlang Xie1Zihan Deng2Hongbo Ai3Tingwen Xiang4Xiaojing Yan5Zhiguo Ling6Shiyu Xiao7Yong Tang8Gang Huang9Fei Luo10Yueqi Chen11Department of Orthopedics, Southwest Hospital, Third Military Medical University, (Army Medical University)Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Third Military Medical University (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University, (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University, (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University, (Army Medical University)Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Third Military Medical University (Army Medical University)Institute of Immunology, PLA, Third Military Medical University (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University, (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University, (Army Medical University)Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Third Military Medical University (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University, (Army Medical University)Department of Orthopedics, Southwest Hospital, Third Military Medical University, (Army Medical University)Abstract Dysbiosis of gut microbiota significantly exacerbates the progression of rheumatoid arthritis (RA). Targeting gut microbiota may present a promising therapeutic strategy for RA. Gold nanospheres (GNS), known for excellent biocompatibility, stability and minimal toxicity, have emerged as precise modulators of gut microbiota, reshaping intestinal environments to treat various inflammatory diseases. Our study found that oral administration of 60-nm GNS effectively ameliorated collagen-induced arthritis (CIA) in mice, with a marked reduction in disease severity and synovial inflammation. Specifically, GNS notably enriched the probiotic genus Ligilactobacillus while restoring intestinal barrier function by upregulating tight junction proteins Claudin-1 and ZO-1. Targeted metabolomics analysis revealed GNS substantially increased the production of indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in gut, which were shown to activate the aryl hydrocarbon receptor (AhR) pathway. Mechanistic studies demonstrated that the IPA/IAA mixture inhibited PTEN ubiquitination, stabilizing PTEN protein levels and suppressing NF-κB activation in synovial tissues. These changes correlated with reduced synovial hyperplasia and inflammatory infiltration. Our findings established GNS as an effective nanomodulator of the gut-joint axis, providing novel insights into microbiota-targeted therapies for RA and other inflammatory diseases. Graphical abstracthttps://doi.org/10.1186/s12951-025-03450-7Rheumatoid arthritis (RA)Gold nanospheres (GNS)Gut microbiotaTryptophan metabolismFibroblast-like synoviocytes (FLSs) |
| spellingShingle | Chuan Yang Langlang Xie Zihan Deng Hongbo Ai Tingwen Xiang Xiaojing Yan Zhiguo Ling Shiyu Xiao Yong Tang Gang Huang Fei Luo Yueqi Chen An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism Journal of Nanobiotechnology Rheumatoid arthritis (RA) Gold nanospheres (GNS) Gut microbiota Tryptophan metabolism Fibroblast-like synoviocytes (FLSs) |
| title | An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism |
| title_full | An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism |
| title_fullStr | An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism |
| title_full_unstemmed | An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism |
| title_short | An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism |
| title_sort | orally administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re shaping gut microbial tryptophan metabolism |
| topic | Rheumatoid arthritis (RA) Gold nanospheres (GNS) Gut microbiota Tryptophan metabolism Fibroblast-like synoviocytes (FLSs) |
| url | https://doi.org/10.1186/s12951-025-03450-7 |
| work_keys_str_mv | AT chuanyang anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT langlangxie anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT zihandeng anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT hongboai anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT tingwenxiang anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT xiaojingyan anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT zhiguoling anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT shiyuxiao anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT yongtang anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT ganghuang anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT feiluo anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT yueqichen anorallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT chuanyang orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT langlangxie orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT zihandeng orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT hongboai orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT tingwenxiang orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT xiaojingyan orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT zhiguoling orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT shiyuxiao orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT yongtang orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT ganghuang orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT feiluo orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism AT yueqichen orallyadministerednanotherapeuticswithgoldnanospheressupplyingforrheumatoidarthritistherapybyreshapinggutmicrobialtryptophanmetabolism |